Selective cyanoethylation of mercaptoamines



Patented Dec. 24, ldfi varsoarnrrarrou or Conn, sssignors to a N.Y-, 19: 9":

-- 1 4, 195a, Ser. No. assess 4 Claims. (Cl. 260-4655) The presentinvention relates to a process for preparing S-cyanoethylatedderivatives of aliphatic mercaptoamines to the roducts thus produce-d.More particularly, it es to :srocess for the selective cyanoethylationof ratio mercaptoamines both substituted and unsubstiand to thecompounds thus obtained.

,lonitrile is an exceptionally versatile chemical raw material. It hasbeen used to introduce the cyanoethyl group (-CH CI' CN) into a largenumber of organic compounds con lining a reactive hydrogen atom. Thus,

example, ierous reactants which have been cyanoethylated include, interalia, various alcohols, aldehydes, amides, amines, esters, lretones,mercapians and other 1 ng a reactive hydrogen atom.

aatic a. 7 is cyanoethylated by acryloa [i-alayiarninopro onitrile isproduced. In most cata st is not required for the reaction which ee bothat low and at high temperatures. When :an is cyanoethylated byacrylonitrile a ti-cyanoalfide is obtained. This cyanoethylationreaction s readily at temperatures below C. and usually procee in the Itis thus re 'ly apparent that since both the amino group the rncrcaptogroup are easily cyanoethylated, extreme difficulty is encountered inintroducing a cyanoethyl group into a mercaptoamine solely andexclusively on the sulfur atom. Now, according to the present invention,we have discovered a process for the selective c anocthylation ofmercaptans containing an amino group lic. g a reactive hydrogen atomwhich overcomes the problems and difficulties inherent in the processesof the prior art.

it has now also been found that by the selective cyanoe lation ofmercaptoamines in accordance with the oi the present invention new anduseful com- {301E138 ma be prepared. lhese compounds may be representedby the following structural formula:

or) l r n n 1 i o o 40112011200011 R R! RI! in which R, R, R", and xhave the same meaning as above and R is a member selected from the groupconsisting of H, alkali metals and lower allcyl radicals.

We have now discovered that substituted or unsubstituted a inhaticmercaptoamines or their salts, e.g., hy-

s, hydrobromides, hydriodides, sulfates and the selectivelycyanoethylatcd with acrylonitrile droc lorice may be in an aqueous orother solvent in the pH range of from about 1 to about 7 and preferablyin the pH range of from about 3.2 to about 6.9. Surprisingly, themercaptoamines react with acrylonitrile exclusively on the sulfhydrylgroup to give good yields of the S-cyanoethyl derivative. While we donot wish to be bound by any particular theory as to the reasons for suchselective cyan ethylation taking place solely on the sulfhydryl group itis believed that the free base of the mercaptoamine exists as internalsalt, a zwitter-ion. Thus, in strongly acid solution the ammonium saltis thought to predomiand cyanoethylation either would not occur or wouldtake place slowly and exclusively on sulfur. However, as the pi l isincreased more of the zwitter-ion would be formed and addition shouldoccur rapidly and exclusively on the mercaptide anion. Finally, in basicsolution wherein the free amine would be present, the reaction withacrylor1i""ile would be rapid but completely non-selective and adiihculty separable mixture of products as a result of cyanoethylationof the free amino groups with either one or two moles of acrylonitrileis obtained.

These novel S-cyanoethylated derivatives of aliphatic mercaptoaminesprepared according to the teachings of the present invention may be usedin a variety of appli 'ations e.g. as i termediates, sequesterants,surface active agents, antioxidants, antistatic agents and the like.

Among the numerous aliphatic mercaptoamines and arious salts thereof,which may be selectively cyanoethylated by the process of our inventionare 2-mercaptoethylamine, 2-mercaptopropylamine, S-mercaptopropylamine,mercaptoaminopropionic acid, mercaptoamino phenyl propionic acid,Z-rnercapto-l-amino-isovaleric acid, 3- mercapto-l-aminobutyric acid,etc.

While an aqueous solvent is preferably employed in the process of thisinvention, it is possible to employ other solvents or diluents as thereaction medium provided, of course, that such solvents do not reactwith the reaction components. As examples of such sta lo and inertsolvents or diluents there may be mentioned, inter alia, ethers,halogenated hydrocarbons, and aliphatic, cycloaliphatic and aromatichydrocarbons.

The reaction of acrylonitrile with an aliphatic mercaptoamine may takeplace at any suitable and convenient temperature from about 10 to about90 C. Generally, however, the reaction is conducted at temperature fromabout 26 to about C. During the course of the reaction, which is highlyexothermic, it may or may not be necessary to cool the reaction mixtureeither by external means or by controlling the rate of addition ofacrylonitrile.

The nature of the invention is further illustrated by the followingnon-limiting examples in which all parts given are by weight unlessotherwise specified:

Example I To a stirred solution of 34 parts (0.3 mol) ofZ-mercaptoethylamine hydrochloride in 100 parts of Water (pl-1:36) areadded 40 parts (0.75 mol) of acrylonitrile in one portion. A mildlyexothermic reaction ensues and the temperatures of the reaction mixturerises to 365 C. after 30 minutes. At the end of minutes, the water andunreacted acrylonitrile are removed under reduced pressure (15 min/ C.)and the resulting syrup is flushed with parts of absolute ethanol andthen with two 100 part portions of an equal mixture of ethanolbenzene.The resulting syrup is crystallized from ethanolbenzene to yield 69% of3-(Z-aminoethylthio)propionitrile hydrochloride as colorless crystals,M.P. 81.3- 83.l C. Upon neutralization of the salt with sodium hydroxide3-(Z-aminoethylthio)-propionitrile is obtained.

Example I] A solution prepared as in Example I is adjusted to pH 6 With1 N sodium hydroxide and then 40 parts (0.75 mol) of acrylonitrile areadded at once. A rapid exothermic reaction takes place and after 6minutes the temperature of the reaction mixture is 52 C. After 60minutes the reaction mixture is made distinctly acidic With hydrochloricacid and then vacuum concentrated and treated as previously described. Ayield of 81.4% of crystalline product, 3-(2-aminoethylthio)propionitrilehydrochloride, M.P. 82.5-84.3" C., is obtained. After neutralization ofthe acid salt With sodium hydroxide, 3-(2-aminoethylthio)propionitrileis obtained.

Example III A solution prepared as in Example I is adjusted to pH 6.8with 1 N sodium hydroxide and 63.6 parts (1.2 mol) of acrylonitrile areadded at once. Again, a strongly exothermic reaction occurs and Within45 seconds the temperature of the reaction mixture is 52 C. After 60minutes the reaction mixture is acidified With hydrochloric acid andthen vacuum concentrated and treated as previously described. A yield of77.8% of colorless crystals of 3-(2-aminoethylthio)propionitrilehydrochloride, MP. 77.578.8 C., is obtained and upon subsequent neutralization of the acid salt 3-(2-arninoethylthio) propionitrile is produced.

Analysis of acid salt.Calculated for C H N SCl: C, 36.03; H, 6.65; N,16.81. Found: C, 35.96; H, 6.62; N, 16.55.

PREPARATION OF 3 Z-AMINOETHYLTHIO PRO PIONIC ACID HYDROCHLORIDE ExampleIV A solution of 33.3 parts of (0.2 mole) of3-(2-aminoethylthio)-propionitrile hydrochloride in 50 parts ofconcentrated hydrochloric acid is heated under reflux for three hours.The resulting solution is vacuum concentrated to a syrup which is thendissolved in 100 parts of boiling, absolute ethanol. After removal ofthe precipitated ammonium chloride, the filtrate is again vacuumconcentrated. Successive treatments with ethanol-benzene and benzene,and subsequent recrystallization from ethanol-hexane yields 73.8% ofcolorless crystals of 3-(2- aminoethylthio)propionic acid hydrochloride,M.P. 120.5122.2. Upon neutralization with sodium carbon; ate,3-(2-aminoethylthio)propionic acid is obtained.

Analysis of acid salt.Calculated for C H ClNO S: C, 32.34; H, 6.52; N,7.55; S, 17.27; Cl, 19.10. Found: C, 32.55; H, 6.72; N, 7.83; S, 17.33;Cl, 18.8

We claim:

1. A process for the preparation of a compound of the formula:

II rt HzN-C-[ ]SCH2CII2CN it 1v in Which R and R" are each selected fromthe group consisting of hydrogen and lower alkyl radicals and x is aninteger at least equal to 1 and not greater than 2 which comprisesreacting an aliphatic niercaptoaniine of the formula:

III Ell H2NC- O -SII l,

claim 1 in which the pH is from References Cited in the tile of thispatent UNITED STATES PATENTS 2,327,119 Martin Aug. 17, 1943 2,439,534Vlilkes Apr. 13, 1948 2,485,236 Gresham et a1. Oct. 18, 1949 2,511,487Thompson June 13, 1950 2,712,553 Feltzin July 5, 1955 2,732,400 WeissJan. 24, 1956 2,823,222 Sexton Feb. 11, 1953 OTHER REFERENCES Bruson:Organic Reactions, volume 5, 1949, pages 79, 95, 96 and 97.

Barkenbus et a1.: J. of Org. Chem., vol. 20, 1955, page ChemicalAbstracts, vol. 50, 1956, page 1980s,

1. A PROCESS FOR THE PREPARATION OF A COMPOUND OF THE FORMULA: